Cortistatin is a putative novel neuropeptide that has a strong similarity to somatostatin and selectively induces slow wave sleep presumably by antagonizing the effects of the neurotransmitter acetylcholine on cortical excitability. Preprocortistatin is exclusively expressed in a subset of cortical and hippocampal interneurons that utilize GABA as their neurotransmitter. Total sleep deprivation increases the steady state levels of preprocortistatin mRNA up to four fold. The number of cortistatin expressing cells in the cerebral cortex is increased in aged animals. This proposal will investigate whether the response to sleep deprivation is preserved in old animals. The pattern of expression of cortistatin and other molecular markers will be examined in sleep deprived aged rats by in situ hybridization. To determine whether increased levels of cortistatin expression result in alterations in the sleep/wake cycle, transgenic mice that overexpress cortistatin will be recorded and their sleep patterns analyzed. These studies will give insight into the function of cortistatin in sleep and may yield therapeutic applications and a better understanding of human sleep disorders in which cortical activity is affected.